• D O Kessel, D C Berridge, and I Robertson.
• Department of Clinical Radiology, Leeds Teaching Hospitals Trust, Beckett Street, Leeds, West Yorkshire, UK, LS9 7TS.
• Cochrane Db Syst Rev. 2004 Jan 1 (1): CD000985.

BackgroundThrombolytic therapy is a useful tool in the management of acute peripheral arterial ischaemia. Fibrinolytic drugs are used to disperse blood clot to clear arterial occlusion. A variety of techniques are used to deliver these agents.ObjectivesTo determine the optimal technique for infusion of fibrinolytic drugs in peripheral arterial ischaemia.Search StrategyThe Cochrane Library (issue 3, 2003) and the Specialised Trials Register of the Cochrane Review Group on Peripheral Vascular Diseases (July 2003) were searched. Proceedings from meetings of British, European and North American Vascular Surgical and Radiological Societies, plus reference lists of identified studies were also searched for relevant trials. Major pharmaceutical firms and trialists were asked about unpublished trials.Selection CriteriaTwo reviewers independently selected randomised controlled trials comparing infusion techniques of fibrinolytic agents in the treatment of acute peripheral arterial ischaemia. Trials with poor quality methodology were excluded.Data Collection And AnalysisData from included trials were collated and analysed for the following outcomes: limb salvage, amputation, death, vessel patency, time to achieve thrombolysis, and reduction in the need for surgical intervention. Complication rates were compared for: major haemorrhage, cerebrovascular accident and distal embolization.Main ResultsIntra-arterial delivery of thrombolytic agents appeared to be more effective than intravenous administration. Thrombolysis was more effective when the angiographic catheter was placed within the thrombus. Although 'high dose' and 'forced infusion' techniques achieved vessel patency in less time than 'low dose infusion', there were more bleeding complications, and no increase in patency rates or improvement in limb salvage at 30 days.Reviewer's ConclusionsImplications for practice Thrombolysis should be reserved for patients with limb threatening ischaemia, due to the high risk of haemorrhage or death. Greater benefit is seen when the thrombolytic agent is delivered into the thrombus. Systemic intravenous thrombolysis is less effective than intra-arterial thrombolysis and is associated with an increase in bleeding complications. 'High dose' and 'forced infusion' techniques, or adjunctive agents such as platelet glycoprotein IIb/IIIa inhibitors may speed up thrombolysis, but these are not accompanied by lower amputation rates or a decreased need for adjunctive endovascular or surgical procedures. 'Low dose continuous infusion', following initial lacing of the thrombus with a high dose of the thrombolytic agent, is the least labour intensive technique. Implications for research Only large multicentre trials with carefully controlled inclusion criteria will be sufficiently powerful to demonstrate genuine benefit for a particular thrombolytic regime.

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